An indirect comparison meta-analysis of AS03 and MF59 adjuvants in pandemic influenza A(H1N1)pdm09 vaccines

Abstract

Background: Although oil-in-water adjuvants improve pandemic influenza vaccine efficacy, AS03 versus MF59 adjuvant comparisons in A(H1N1)pdm09 pandemic vaccines are lacking.

Methods: We conducted an indirect-comparison meta-analysis extracting published data from randomised controlled trials in literature databases (01/01/2009-09/09/2018), evaluating immunogenicity and safety of AS03- or MF59-adjuvanted vaccines. We conducted comparisons of log-transformed haemagglutination inhibition geometric mean titre ratio (GMTR; primary outcome) of different regimens of each adjuvant versus unadjuvanted counterparts. Then via test of subgroup differences, we indirectly compared different AS03 versus MF59 regimens.

Results: We identified 22 publications with 10,734 participants. In adults, AS03-adjuvanted vaccines (3.75 µg haemagglutinin) achieved superior GMTR versus unadjuvanted vaccines (all four comparisons); MD = 0.56 (95%CI 0.33 to 0.80, p < 0.001) to 1.18 (95%CI 0.72 to 1.65, p < 0.001). MF59 (full-dose)-adjuvanted vaccines (7.5 µg haemagglutinin) were superior to unadjuvanted vaccines (three of four comparisons); MD = 0.47 (95%CI 0.19 to 0.75, p = 0.001) to 0.80 (95%CI 0.44 to 1.16, p < 0.001). Adult indirect comparisons favoured AS03 over MF59 (six of eight comparisons; p < 0.001 to p = 0.088). Paediatric indirect comparisons favoured MF59-adjuvanted vaccines (two of seven comparisons; p = 0.011, 0.079). However, unadjuvanted control group seroconversion rate was lower in MF59 than AS03 studies (p < 0.001 to p = 0.097). There was substantial heterogeneity, and adult AS03 studies had lower risk of bias.

Conclusions: Despite limited studies, in adults, AS03-adjuvanted vaccines allow antigen sparing versus MF59-adjuvanted and unadjuvanted vaccines, with similar immunogenicity, but higher risk of pain and fatigue (secondary outcomes) than unadjuvanted vaccines. In children, adjuvanted vaccines are also superior, but the better adjuvant is uncertain.

Keywords: Adjuvants; H1N1 subtype; Immunologic; Influenza A virus; Influenza vaccines; Meta-analysis; Pandemics.